Evolution of lasR mutants in polymorphic Pseudomonas aeruginosa populations facilitates chronic infection of the lung

Kelei Zhao (), Xiting Yang, Qianglin Zeng, Yige Zhang, Heyue Li, Chaochao Yan, Jing Shirley Li, Huan Liu, Liangming Du, Yi Wu, Gui Huang, Ting Huang, Yamei Zhang, Hui Zhou, Xinrong Wang, Yiwen Chu () and Xikun Zhou ()
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Kelei Zhao: Affiliated Hospital of Chengdu University, Chengdu University
Xiting Yang: Affiliated Hospital of Chengdu University, Chengdu University
Qianglin Zeng: Affiliated Hospital of Chengdu University, Chengdu University
Yige Zhang: Sichuan University
Heyue Li: Sichuan University
Chaochao Yan: Chinese Academy of Sciences
Jing Shirley Li: Sichuan University
Huan Liu: Sichuan University
Liangming Du: Affiliated Hospital of Chengdu University, Chengdu University
Yi Wu: Affiliated Hospital of Chengdu University, Chengdu University
Gui Huang: Affiliated Hospital of Chengdu University, Chengdu University
Ting Huang: Affiliated Hospital of Chengdu University, Chengdu University
Yamei Zhang: Affiliated Hospital of Chengdu University, Chengdu University
Hui Zhou: Affiliated Hospital of Chengdu University, Chengdu University
Xinrong Wang: Affiliated Hospital of Chengdu University, Chengdu University
Yiwen Chu: Affiliated Hospital of Chengdu University, Chengdu University
Xikun Zhou: Sichuan University

Nature Communications, 2023, vol. 14, issue 1, 1-14

Abstract: Abstract Chronic infection with the bacterial pathogen Pseudomonas aeruginosa often leads to coexistence of heterogeneous populations carrying diverse mutations. In particular, loss-of-function mutations affecting the quorum-sensing regulator LasR are often found in bacteria isolated from patients with lung chronic infection and cystic fibrosis. Here, we study the evolutionary dynamics of polymorphic P. aeruginosa populations using isolates longitudinally collected from patients with chronic obstructive pulmonary disease (COPD). We find that isolates deficient in production of different sharable extracellular products are sequentially selected in COPD airways, and lasR mutants appear to be selected first due to their quorum-sensing defects. Polymorphic populations including lasR mutants display survival advantages in animal models of infection and modulate immune responses. Our study sheds light on the multistage evolution of P. aeruginosa populations during their adaptation to host lungs.

Date: 2023
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DOI: 10.1038/s41467-023-41704-w

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